Hereditary Sensory and Autonomic Neuropathies (HSAN)

What hereditary sensory neuropathies are

Peripheral nerves carry three kinds of signal: motor (movement), sensory (touch, pain, temperature, position) and autonomic (automatic functions such as sweating and blood pressure). In HSAN, a gene change damages mainly the sensory and autonomic nerve fibers, especially the small fibers that carry pain and temperature.

This sets HSAN apart from Charcot-Marie-Tooth disease, the most common inherited neuropathy, which affects mostly motor and sensory fibers and causes weakness and foot deformities. Some genes cause overlapping features of both.

Types of HSAN

HSAN I is the most common type in adults. It is linked to genes such as SPTLC1. Familial dysautonomia is caused by changes in the ELP1 gene and is most common in people of Ashkenazi Jewish descent. HSAN IV is caused by changes in NTRK1 and HSAN V by changes in NGF. Changes in the SCN9A gene cause a separate condition, congenital insensitivity to pain, with similar effects.

Symptoms

Adult-onset forms (mainly HSAN I)

• numbness in the feet that slowly spreads up the legs, later sometimes the hands
• loss of the ability to feel hot and cold, leading to burns from bathwater or heaters
• sharp, shooting or burning pains in the legs
• painless blisters, calluses and ulcers on the soles
• foot infections that can spread to the bone (osteomyelitis)
• reduced sweating in the feet
• in some families, hearing loss or memory problems

Childhood-onset forms

• a baby who does not cry with injuries or vaccinations
• biting the tongue, lips or fingers, sometimes causing serious wounds
• repeated fractures and joint injuries that are noticed late
• self-amputation of finger or toe tips in severe types
• unexplained fevers and overheating if the child cannot sweat
• in familial dysautonomia: no tears when crying, poor sucking and swallowing, frequent pneumonia from inhaling food, vomiting crises and big swings in blood pressure

Complications

• chronic foot ulcers and infections
• bone infection and amputation
• Charcot joints: painless joint destruction in the ankle or foot from repeated unnoticed injury
• unrecognized fractures and burns
• eye damage from absent tears and reduced corneal sensation (in some types)
• heat stroke in people who cannot sweat

How it is diagnosed

1. History and family tree: the age symptoms began, injuries, sweating and tear production, and similar problems in relatives.
2. Neurological exam: testing light touch, pinprick, vibration, temperature, reflexes and strength.
3. Nerve conduction studies and EMG: show reduced or absent sensory nerve signals. Small-fiber forms may need other tests.
4. Skin biopsy: counts small nerve fibers in a tiny skin sample.
5. Autonomic tests: sweat testing, blood pressure responses and, in familial dysautonomia, an absent skin flare after a histamine injection.
6. Genetic testing: a blood test with a neuropathy gene panel confirms the type in many people.

Doctors also rule out acquired causes that look similar, such as diabetes, vitamin B12 deficiency, alcohol and leprosy.

Treatment and daily management

There is no treatment that repairs the nerves yet, so care focuses on preventing injury and treating complications early.

Foot and skin protection

• Check your feet every day, including between the toes, with a mirror if needed.
• Wear well-fitted, cushioned shoes and socks at all times, including indoors.
• Test bathwater with an elbow or thermometer, and keep away from heaters and hot surfaces.
• See a podiatrist regularly to manage calluses and nails.
• Treat any blister or wound promptly, and rest the foot. Offloading boots or casts help ulcers heal.

Pain

People with HSAN I often have shooting or burning pain. Medicines for neuropathic pain, such as gabapentin, pregabalin or some antidepressants, can help.

Children with insensitivity to pain

• Regular checks for hidden fractures and joint injuries.
• Dental care, and sometimes mouthguards or tooth smoothing, to limit tongue and lip biting.
• Cooling strategies and close temperature monitoring for children who cannot sweat.
• Eye lubricants for children with reduced tears.

Familial dysautonomia

Care is coordinated at specialist centers and includes feeding support, eye drops, blood pressure medicines and treatment plans for vomiting crises.

Genetic counseling

Because these conditions are inherited, relatives may wish to be tested. Genetic counseling explains the chance of passing it on and options for future pregnancies.

Outlook

HSAN I usually progresses slowly over decades, and life expectancy is normal when foot problems are prevented. Outlook in the childhood forms depends on the type and the severity of injuries and infections. Specialist care has improved survival and quality of life in familial dysautonomia.

Frequently asked questions

What is hereditary sensory and autonomic neuropathy?

It is a group of rare inherited conditions in which the nerves that carry pain, temperature and touch, and sometimes those that control sweating, tears and blood pressure, do not work properly. The main danger is unnoticed injuries, burns and infections, especially in the feet.

What are the types of HSAN?

There are five classic types. Type I starts in adolescence or adulthood with numb feet and ulcers. Type II starts in childhood with widespread sensory loss. Type III is familial dysautonomia. Type IV is congenital insensitivity to pain with no sweating. Type V causes pain insensitivity with normal sweating.

Is hereditary sensory neuropathy the same as Charcot-Marie-Tooth disease?

No, but they are related. Charcot-Marie-Tooth disease mainly affects motor and sensory nerves, causing weakness, foot deformities and balance problems. HSAN mainly affects sensation and autonomic function, with little weakness. Some gene changes produce features of both.

Can people with HSAN feel pain at all?

It depends on the type. In HSAN I, pain sensation is reduced in the feet, yet many people have spontaneous shooting or burning pains. In types IV and V, children are born unable to feel pain, which is why they injure themselves without realizing it.

Is there a cure for hereditary sensory neuropathy?

Not yet. Treatment focuses on protecting the feet and hands, treating wounds and infections early, controlling nerve pain, and managing autonomic problems. Research into gene-based therapies is ongoing, particularly for familial dysautonomia.